The National Institute for Occupational Safety and Health estimates that there are 30 million American workers exposed to hazardous noise, with 1/3rd of those workers suffering from a detectable noise-induced hearing loss. Noise-induced hearing loss is the most common occupational injury in the U.S. Erway et al. (1996) showed that the C57BL/6J strain of mice were more susceptible to noise damage than the CBA/CaJ strain of mice and this difference was genetic in origin. Davis et al. (1999) developed a noise- dose response curve for the two strains and showed that, not only were C57BL/6J mice about 8 dB more sensitive to noise, their dose-response curve had a different slope than CBA/CaJ. This implied that there were two different mechanisms responsible for cochlear damage. Much is known about how very loud sounds damage hearing in chinchillas. The EPA estimates that 80% of workers are exposed to less than 90 dBA of noise. These levels are assumed to be safe by regulation. The proposal is designed to look at the boundary between noise that causes only repairable, temporary threshold shift (TTS) and noise that causes permanent damage to the cochlea, or permanent threshold shift (PTS). CBA mice will be exposed short-term to noise levels that produce TTS or PTS. By looking at the changes in expression of RNA and proteins after exposure we can identify markers of the boundary of TTS and PTS. We propose to explore the use of Laser Capture Microdissection (LCM) technique to target the expression analysis to cells within specific functional domains of the cochlea after noise exposure. Protein and mRNA expression will be analyzed immediately after exposure to noise to determine how the permanent threshold shift develops. Noise-induced hearing loss is the most common occupational injury in the U.S. This proposal is designed to look at the boundary between noise that causes only repairable, temporary threshold shift (TTS) and noise that causes permanent damage to the cochlea, or permanent threshold shift (PTS) in the laboratory mouse. [unreadable] [unreadable] [unreadable]